The Resuscitation Outcomes Consortium (ROC) will conduct the Prospective, Randomized, Optimal Platelet and Plasma Ratios (PROPPR) Phase III trial to compare 24-hour and 30-day mortality (co-primary outcomes) in 580 subjects receiving differing blood product ratios. Subjects in PROPPR must meet eligibility criteria and be predicted to receive a massive transfusion (MT) within 24 hours of emergency admission to a Level I Adult Trauma Center. The trial begins with a Vanguard Stage (120 subjects) conducted in at least four sites to study two ratios (1:1:2, 1:1:3, plasma:platelets:RBCs) and choose the better arm to carry forward into Phase III to compare to 1:1:1. The closest equivalent to whole blood. 40 subjects per arm, provide 83% probability of correctly choosing the better arm. In the Vanguard Stage, we will assess protocol safety, feasibility and begin study of trauma induced coagulopathy (TIC) and inflammatory markers. In Phase III, 580 total subjects (including 80 from the Vanguard Stage), provide 90% power to detect a difference of 10% or more in 24-hour mortality and 88% power to detect a difference of 12% or more in 30-day mortality, assuming each alpha=0.044, two-sided test, and 11% 24-hour mortality and 23% 30-day mortality in the 1:1:1 group. Mantel-Haenszel tests will be used with site as a stratifying variable. We will describe mechanistic drivers and sequelae of TIC and inflammation, and characterize the natural history of the coagulation milieu with resuscitation after severe injury in randomized patients. Given the life-threatening situation and the prospect of benefit in each treatment arm, exception from informed consent will be used. Susanne May, ROC Data Coordinating Center (DCC), is the Principal Investigator (PI) of contact. Gerald van Belle, DCC, is the PI-PROPPR. John Holcomb is PI of the UTHealth Clinical Coordinating Center, a ROC satellite, supervises the Clinical Sites, as well as the laboratory and systems biology components. Barbara Tilley of The UTHealth School of Public Health is the PI of the Data Coordinating Center, a ROC satellite, manages the data, oversees data quality, provides analyses of blinded and unblinded data, provides on-site study monitors, and reports on safety and interim analyses to the Data Safety Monitoring Committee. RELEVANCE: The knowledge gained from this Phase III trial will impact the way in which massively bleeding patients at hospitals are transfused. By making better decisions regarding which patients are most in need of a massive transfusion, and transfusing the right ratio of blood products to mitigate potential traumatic coagulopathies, trauma teams will be afforded an ability to impact populations and lower the amount of otherwise preventable deaths resulting from hemorrhagic shock.